Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

Abstract

A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent.

• Authors: Trond Myhrer, Espen Mariussen, Siri Enger, Pål Aas
• Journal: Neurotoxicology (Neurotoxicology) Vol. 50 Pg. 142-8 (Sep 2015) ISSN: 1872-9711 [Electronic] Netherlands
• PMID: 26318504 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anticonvulsants
• Antidotes
• Nerve Agents
• Organophosphates
• Organophosphorus Compounds
• Organothiophosphorus Compounds
• Oximes
• Pyridinium Compounds
• Levetiracetam
• Soman
• VX
• Procyclidine
• asoxime chloride
• tabun
• cyclohexyl methylphosphonofluoridate
• Piracetam

Topics

• Animals
• Anticonvulsants (therapeutic use)
• Antidotes (therapeutic use)
• Body Weight (drug effects)
• Brain (drug effects, pathology, physiopathology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electroencephalography
• Lethal Dose 50
• Levetiracetam
• Male
• Nerve Agents (toxicity)
• Organophosphate Poisoning (drug therapy, etiology)
• Organophosphates (toxicity)
• Organophosphorus Compounds (toxicity)
• Organothiophosphorus Compounds (toxicity)
• Oximes (therapeutic use)
• Piracetam (analogs & derivatives, therapeutic use)
• Procyclidine (therapeutic use)
• Pyridinium Compounds (therapeutic use)
• Rats
• Rats, Wistar
• Seizures (chemically induced, drug therapy)
• Soman (toxicity)